Small-Scale Approaches

As previously noted, the usual purpose of these methods is to provide relatively small amounts of material, in a rapid maimer, with little risk of the chemistry failing. Cost is not of primary concern. One of the methods cited in the following sections for larger-scale approaches may be applicable for the product candidate, but experience with these methodologies has to be such that success can be attained in a synthesis campaign with little work involved in the transfer of technology to this project. 

One of tlie most general approaches available is to use a chiral auxiliary, because many examples arc available in the literature and the scope and limitations of the various structures available as auxiliary units has been documented (see also Chapter 14) [4—6]. 

This class of compounds serves as a chiral template rather than a chiral auxiliary, as the original stereogenic center is destroyed in the reaction sequence. 

The preferred auxiliaries in chemistry at NSC Technologies are oxazolidinones. Oxazolidinones have found widespread use as chiral auxiliaries. A wide range of reactions is available and well documented [5], including aldol alkylations oc-substitution with a heteroatom such as halogenation, aminations, hydroxyla-tions, and sulphenylations Diels-Alder cycloadditions and conjugate additions. 

Although our general philosophy is to undertake an asymmetric synthesis, there are occasions when a resolution method can be useful. On the chemical side, this approach usually comes into play when small amounts of material are required and alternative methodology is under development. In contrast, biological approaches can be efficient if a dynamic resolution can be achieved or if the starting materials are very cheap and readily available (see later). 

---

Pavia, D. L. Lampman, G. M. Driz, G. S. Engel, R. G. Introduction to Organic Laboratory Techniques Small Scale Approach Saunders College Publishing Orlando, FL, 1998 p 72. 

C. F. Wilcox, M. F. Experimental Organic Chemistry A Small Scale Approach Prentice Hall New York 1994. (g) Furniss, B. S. Hannaford, A. J. Smith, P. W. G Tatchell, A. R., eds. Vogel s Textbook of Practical Organic Chemistry Longmans London 1989, 5th edn. 

This technique can be used to obtain structural information on very small scales approaching the molecular dimensions. It can be used to study surface morphology, internal structure, and crystallographic analysis. It can provide information about cocrystallization, very fine depression phases, or interfaces. 

One potential problem with this approach is that heat loss from a small scale column is much greater than from a larger diameter column. As a result, small columns tend to operate almost isotherm ally whereas in a large column the system is almost adiabatic. Since the temperature profile in general affects the concentration profile, the LUB may be underestimated unless great care is taken to ensure adiabatic operation of the experimental column. 

Continuously operated, small-scale or pilot-plant thickeners, ranging from 75 mm diameter by 400 mm depth to several meters in diameter, are also effectively used for sizing hill-scale equipment. This approach requires a significantly greater volume of sample, such as... 

As mentioned in Section 2.2 (Fixed-Bed Reactors) and in the Micro activity test example, even fluid-bed catalysts are tested in fixed-bed reactors when working on a small scale. The reason is that the experimental conditions in laboratory fluidized-bed reactors can not even approach that in production units. Even catalyst particle size must be much smaller to get proper fluidization. The reactors of ARCO (Wachtel, et al, 1972) and that of Kraemer and deLasa (1988) are such attempts. 

Peclet number independent of Reynolds number also means that turbulent diffusion or dispersion is directly proportional to the fluid velocity. In general, reactors that are simple in construction, (tubular reactors and adiabatic reactors) approach their ideal condition much better in commercial size then on laboratory scale. On small scale and corresponding low flows, they are handicapped by significant temperature and concentration gradients that are not even well defined. In contrast, recycle reactors and CSTRs come much closer to their ideal state in laboratory sizes than in large equipment. The energy requirement for recycle reaci ors grows with the square of the volume. This limits increases in size or applicable recycle ratios. 

For a new process plant, calculations can be carried out using the heat release and plume flow rate equations outlined in Table 13.16 from a paper by Bender. For the theory to he valid, the hood must he more than two source diameters (or widths for line sources) above the source, and the temperature difference must be less than 110 °C. Experimental results have also been obtained for the case of hood plume eccentricity. These results account for cross drafts which occur within most industrial buildings. The physical and chemical characteristics of the fume and the fume loadings are obtained from published or available data of similar installations or established through laboratory or pilot-plant scale tests. - If exhaust volume requirements must he established accurately, small scale modeling can he used to augment and calibrate the analytical approach. 

Following a similar approach to that used for low-level hcxtds, small-scale modeling is often pursued for the design of canopy hoods for a new facility or for modifications to an existing installation. >-i-24 Bender describes rests carried out... 

Exposure to other ideas, resources and opportunities broadens teachers awareness of possibilities for change and fosters a sense that alternatives are available. Teachers would make use, initially on a small scale, of classroom materials developed especially to meet the new approaches to models of the triplet relationship (see especially Tsaparlis, 2008 Tan et al., 2008 Meijer et al., 2008 Davidowitz Chittleborough, 2008 Justi et al., 2008 Treagust Chandra-segaran, 2008). This awareness of alternative resources implies either that such materials are prepared beforehand (Van Berkel, Pilot, finite, 2008) or that the teachers themselves prepare the materials by an action research approach (Ferk Savec et al., 2008). 

Increased coefficients relating to the conditions of preparation and the handling procedure are then applied. The aim is to quantify the risk in industrial plants. This might be where this approach may appear to be too specialised to be of use in small scale reactions. The table below gives these coefficients. ... 

---